Presentation is loading. Please wait.

Presentation is loading. Please wait.

Galit Ankri-Eliahoo, PhD, Kevin Weitz, BS, Timothy C. Cox, PhD, Gale L

Published byمحمدجواد رودگر Modified over 5 years ago

Similar presentations

Presentation on theme: "Galit Ankri-Eliahoo, PhD, Kevin Weitz, BS, Timothy C. Cox, PhD, Gale L"— Presentation transcript:

1 p27kip1 Knockout enhances collateralization in response to hindlimb ischemia 
Galit Ankri-Eliahoo, PhD, Kevin Weitz, BS, Timothy C. Cox, PhD, Gale L. Tang, MD  Journal of Vascular Surgery  Volume 63, Issue 5, Pages (May 2016) DOI: /j.jvs Copyright © Terms and Conditions

2 Fig 1 Schematic diagram showing the arterial anatomy of the mouse hindlimb. Indicated on the diagram are the femoral area position (just proximal to the ligation); artery positions 1 (proximal saphenous artery), 2 (midsaphenous artery), and 3 (distal saphenous artery); gracilis collateral positions 1 (upstream collateral), 2 (midcollateral), and 3 (downstream collateral); and bridge collateral positions. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © Terms and Conditions

3 Fig 2 p27−/− mice revascularize better than wild-type (wt) control mice. A, Representative serial laser Doppler flux images of the mouse plantar footpads (left, ischemic; right, control) for p27−/− and wt mice measured weekly during 28 days. B, The p27−/− mice (n = 10) had significantly improved blood flow (ischemic/nonischemic ratio) starting at day 7 and continuing through day 28 compared with wt mice (n = 9). *P < .05. POD, Postoperative day. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © Terms and Conditions

4 Fig 3 Bridge collateral diameters significantly increased in p27−/− mice after hindlimb ischemia. A, Representative microcomputed tomography (microCT) scans of the nonischemic and ischemic hindlimbs from a p27−/− and a wild-type (wt) mouse at 28 days after induction of ischemia. The arteries have been digitally pseudocolored to better differentiate the main arteries (1, pink) from defined collateral pathways (2, blue) and other muscle branches (3, red). L, Location of ligation. Bridge collateral pathway denoted with arrow. B, The vessel diameters were measured from the microCT scans (n = 5 p27−/− and n = 4 wt sets of hindlimbs). The graph presents the summary of the different vessel diameters from the ischemic hindlimb. The gracilis collateral diameters were measured at the collateral 1 position, and the bridge collateral diameters were measured at the femoral artery position. *P < .001. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © Terms and Conditions

5 Fig 4 After hindlimb ischemia, p27−/− mice have increased arterial density. A, Arterial number, as measured by microcomputed tomography (microCT) at the femoral artery position of the ischemic hindlimb and expressed as percentage increase over the nonischemic hindlimb, increased more in the p27−/− mice (n = 5) than in the wild-type (wt) mice (n = 4). *P < .03. B, Graph showing the total arterial area as a percentage of total cross-sectional area (both normalized to the uninjured hindlimb) at the femoral artery position. *P < .05. C, Graph quantitating the number of arteries at the femoral position of the ischemic hindlimb above and below 70 μm. The p27−/− mice had significantly more arteries larger than 70 μm than the wt mice did. *P < .02. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © Terms and Conditions

6 Fig 5 Decreasing p27 expression in vascular smooth muscle cells (VSMCs) increases migration. A, Under conditions of growth arrest, the top four panels show representative photomicrographs of a scratch assay using confluent VSMCs derived from p27−/− (left panels) and wild-type (wt) aortae (right panels) in the absence and presence of BB94. The bottom panels show a scratch assay using wt VSMCs transfected with small interfering RNA (siRNA) directed against p27 (left panel) or scrambled siRNA (right panel). The dotted lines mark the edge of cell migration. B, Graph demonstrating the increased migration by p27−/− cells. The wt cells expressing less p27 (through siRNA knockdown) also migrate more than wt cells transfected with scrambled siRNA. BB94 inhibits cell migration by both p27−/− and wt cells. Values are expressed as the percentage of the scratch area after 20 hours from the initial scratch area at t = 0. n = 4 separate experiments using two different cell lines for each group. *P < .01. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © Terms and Conditions

7 Fig 6 p27−/− vascular smooth muscle cells (VSMCs) cause more collagen gel contraction than wild-type (wt) VSMCs do. A, Representative photomicrographs from a collagen gel contraction assay. p27−/− VSMCs were suspended in a collagen gel in the absence and presence of BB94. The pink dashed circles represent the circumference of the collagen gel area measured at time 0 and 20 hours. B, Graph demonstrating the increased collagen gel contraction caused by p27−/− cells, which is inhibited by BB94. Values are expressed as the percentage of collagen gel area after 20 hours from the initial collagen gel area at t = 0. n = 4 experiments. *P < .05. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © Terms and Conditions

8 Fig 7 p27−/− vascular smooth muscle cells (VSMCs) express significantly more matrix metalloproteinase 2 (MMP-2) messenger RNA (mRNA) than wild-type (wt) cells do. The left bars demonstrate that the p27 mRNA expression is effectively knocked out in the isolated p27−/− VSMCs. The right bars show that the p27−/− VSMCs express significantly more MMP-2 mRNA than wt cells do. Relative p27 mRNA expression was normalized to 100% for the wt cells for both genes. *P < .001. Journal of Vascular Surgery  , DOI: ( /j.jvs ) Copyright © Terms and Conditions

Download ppt "Galit Ankri-Eliahoo, PhD, Kevin Weitz, BS, Timothy C. Cox, PhD, Gale L"

Similar presentations

Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular.

Ultrasound-guided percutaneous delivery of tissue-engineered endothelial cells to the adventitia of stented arteries controls the response to vascular.
Matrix Metalloproteinase-9 Deficiency Results in Decreased Fiber Cross-Sectional Area and Alters Fiber Type Distribution in Mouse Hindlimb Skeletal Muscle.

Matrix Metalloproteinase-9 Deficiency Results in Decreased Fiber Cross-Sectional Area and Alters Fiber Type Distribution in Mouse Hindlimb Skeletal Muscle.
Vascular endothelial growth factor-C derived from CD11b+ cells induces therapeutic improvements in a murine model of hind limb ischemia  Go Kuwahara,

Vascular endothelial growth factor-C derived from CD11b+ cells induces therapeutic improvements in a murine model of hind limb ischemia  Go Kuwahara,
Recovery from hind limb ischemia is less effective in type 2 than in type 1 diabetic mice: Roles of endothelial nitric oxide synthase and endothelial.

Recovery from hind limb ischemia is less effective in type 2 than in type 1 diabetic mice: Roles of endothelial nitric oxide synthase and endothelial.
Platelet-derived growth factor C promotes revascularization in ischemic limbs of diabetic mice  Junji Moriya, MD, PhD, Xiumin Wu, PhD, Jose Zavala-Solorio,

Platelet-derived growth factor C promotes revascularization in ischemic limbs of diabetic mice  Junji Moriya, MD, PhD, Xiumin Wu, PhD, Jose Zavala-Solorio,
High mobility group box 1 promotes endothelial cell angiogenic behavior in vitro and improves muscle perfusion in vivo in response to ischemic injury 

High mobility group box 1 promotes endothelial cell angiogenic behavior in vitro and improves muscle perfusion in vivo in response to ischemic injury 
Dipeptidyl peptidase 4 inhibitor reduces intimal hyperplasia in rabbit autologous jugular vein graft under poor distal runoff  Akio Koyama, MD, Kimihiro.

Dipeptidyl peptidase 4 inhibitor reduces intimal hyperplasia in rabbit autologous jugular vein graft under poor distal runoff  Akio Koyama, MD, Kimihiro.
Reduced hind limb ischemia-reperfusion injury in Toll-like receptor-4 mutant mice is associated with decreased neutrophil extracellular traps  Rahmi Oklu,

Reduced hind limb ischemia-reperfusion injury in Toll-like receptor-4 mutant mice is associated with decreased neutrophil extracellular traps  Rahmi Oklu,
Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms  Xuan Zhang, PhD, Sean Thatcher, PhD,

Castration of male mice prevents the progression of established angiotensin II-induced abdominal aortic aneurysms  Xuan Zhang, PhD, Sean Thatcher, PhD,
In vivo electroporation of constitutively expressed HIF-1α plasmid DNA improves neovascularization in a mouse model of limb ischemia  Geoffrey O. Ouma,

In vivo electroporation of constitutively expressed HIF-1α plasmid DNA improves neovascularization in a mouse model of limb ischemia  Geoffrey O. Ouma,
Ulka Sachdev, MD, Xiangdong Cui, MS, Edith Tzeng, MD 

Ulka Sachdev, MD, Xiangdong Cui, MS, Edith Tzeng, MD 
Zinc finger protein 191 deficiency attenuates vascular smooth muscle cell proliferation, migration, and intimal hyperplasia after endovascular arterial.

Zinc finger protein 191 deficiency attenuates vascular smooth muscle cell proliferation, migration, and intimal hyperplasia after endovascular arterial.
Elevation of hemopexin-like fragment of matrix metalloproteinase-2 tissue levels inhibits ischemic wound healing and angiogenesis  April E. Nedeau, MD,

Elevation of hemopexin-like fragment of matrix metalloproteinase-2 tissue levels inhibits ischemic wound healing and angiogenesis  April E. Nedeau, MD,
Hyperglycemia limits experimental aortic aneurysm progression

Hyperglycemia limits experimental aortic aneurysm progression
Xue Ma, MD, Jeffrey D. Pearce, MD, David B. Wilson, MD, William P

Xue Ma, MD, Jeffrey D. Pearce, MD, David B. Wilson, MD, William P
An engineered vascular endothelial growth factor-activating transcription factor induces therapeutic angiogenesis in ApoE knockout mice with hindlimb.

An engineered vascular endothelial growth factor-activating transcription factor induces therapeutic angiogenesis in ApoE knockout mice with hindlimb.
Smooth muscle cells from abdominal aortic aneurysms are unique and can independently and synergistically degrade insoluble elastin  Nathan Airhart, MD,

Smooth muscle cells from abdominal aortic aneurysms are unique and can independently and synergistically degrade insoluble elastin  Nathan Airhart, MD,
The bone marrow-derived endothelial progenitor cell response is impaired in delayed wound healing from ischemia  Stephen M. Bauer, MD, Lee J. Goldstein,

The bone marrow-derived endothelial progenitor cell response is impaired in delayed wound healing from ischemia  Stephen M. Bauer, MD, Lee J. Goldstein,
Coarctation-induced degenerative abdominal aortic aneurysm in a porcine model  Pao-Yen Lin, MD, Yeng-Ting Wu, MS, Guan-Cheng Lin, BS, Yao Hsiang Shih,

Coarctation-induced degenerative abdominal aortic aneurysm in a porcine model  Pao-Yen Lin, MD, Yeng-Ting Wu, MS, Guan-Cheng Lin, BS, Yao Hsiang Shih,
Low molecular weight (LMW) heparin inhibits injury-induced femoral artery remodeling in mouse via upregulating CD44 expression  Gaofeng Zhao, MD, PhD,

Low molecular weight (LMW) heparin inhibits injury-induced femoral artery remodeling in mouse via upregulating CD44 expression  Gaofeng Zhao, MD, PhD,

Similar presentations

Ads by Google